Figure 1.

The σ₁R agonist (+)-pentazocine dose-dependently potentiated cocaine self-administration in rats. A, representative cumulative records of an individual subject responding showing patterns of self-administration in real time maintained by intravenous cocaine when each fifth-response produced an injection (fixed-ratio, or FR 5-response schedule). Ordinates show cumulative responses. Abscissae show time. The five 20-min self-administration components of each session are indicated by a downward displacement of the lowest line below each record. At the end of each component the cumulative-response curve reset to base. The preceding 2-min timeout periods are indicated by the upward position of the lowest line of each record. In the first component, each fifth response turned off the light-emitting diodes for 20 s but did not activate the infusion pump (EXT); in subsequent components, injections were also delivered with each fifth response (diagonal marks on the cumulative record) with doses (in mg/kg/injection) indicated. Vertical marks on the event line below the cumulative curve indicate responses on the left (inactive) lever. The encircled portion of the record in the third component is magnified to better show the temporal pattern of responding. Note the dose-dependent increase in responding up to the cocaine dose of 0.32 mg/kg/injection in the top record and the increases in responding at lower doses of cocaine after pretreatment with 3.2 mg/kg of (+)-pentazocine in the bottom record. In general, (+)-pentazocine affected overall rates without changes in the temporal pattern of responding. B, dose-effect curves of cocaine self-administration and the effect of (+)-pentazocine treatment. Each point represents the mean ± S.E. (n = 6) of response rates maintained during extinction (EXT, responses had no scheduled consequences) or under the FR5 schedule at the indicated cocaine doses/injection. Asterisks indicate significant effects of the doses of i.p. (+)-pentazocine (○, ▵, ▿) compared with saline pretreatment (●) as determined by two-way repeated measures ANOVA and Tukey post-hoc tests (*, p < 0.05; **, p < 0.01; ***, p < 0.001). Note that (+)-pentazocine rendered the subject more sensitive to cocaine dose.